tbuckley/cabot-search huggingface dataset:
Abstract 14669: Type 2 Diabetes and Atrial Fibrillation: Exploring Causal Pathways Using Mendelian Randomization
Authors: Maddalena Ardissino, Rohin K Reddy, Fu Siong Ng
Journal: Circulation (2022)

Introduction: The association between type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF) has been established in observational studies. This has not been replicated in genetic studies, suggesting that it might be driven by confounding. Hypothesis: Mendelian randomization (MR) uses genetic variants as instrumental variables to study casual relationships between exposures and outcomes. We conducted a two-sample multivariable MR study to investigate whether T2DM is causally related to AF risk. Methods: 182 uncorrelated (r 2 &lt;0.001) SNPs associated with T2DM ( p &lt;5х10 –8 ) were extracted from a GWAS on 180,834 affected individuals. Inverse-variance weighted (IVW) MR was used for primary analysis, weighted median and MR-Egger as sensitivity analyses. Radial MR was used to identify outlier SNPs. Potentially pleiotropic phenotypes were identified by phenome-wide scanning of outlier SNPs using MR-TRYX. Multivariable MR adjusting for these phenotypes was then performed. Results: Genetically-predicted T2DM was associated with AF in univariable analysis (IVW OR: 1.08, 95% CI 1.02 - 1.13, p = 0.003). Sensitivity analyses identified pleiotropic effects (MR-Egger intercept p = 0.02). Four outlier SNPs were identified, and these were associated with low-density lipoprotein cholesterol (LDL-C), body-mass index (BMI) and systolic blood pressure (SBP). T2DM remained associated with AF after adjustment for LDL (OR:1.09, 95% CI 1.02-1.16, p = 0.01) and BMI (OR: 1.09, 95% CI 1.01 - 1.17, p = 0.02). However, following adjustment for SBP the relationship between T2DM and AF was fully attenuated (OR: 1.04, 95% CI 0.95 - 1.13, p = 0.40). Conclusions: We took a stepwise approach towards parsing the independent effects of T2DM on AF risk. T2DM was found to be associated with AF through a parallel, pleiotropic genetic pathway influencing SBP. This implies SBP reduction alongside hypoglycaemic therapies may provide particular benefit in reducing AF risk in patients with T2DM.
Abstract 15442: Pharmacological and Atrial Cardiomyocyte-Specific Inhibition of Tumor Necrosis Factor (TNF) Protects Against Adverse Atrial Remodeling and Valvular Atrial Fibrillation an a Mouse Model of Aortic Regurgitation
Authors: Robert Lakin, Xueyan Liu, WENLIANG CHEN, RYAN DEBI, Simona Yakobov, Nazari Polidovitch, Peter Backx
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) is the most common sustained supraventricular arrhythmia worldwide. Most conditions linked to AF, such as cardiovascular (CVD) and valvular disease, are linked to elevated atrial pressures and atrial cardiomyocyte (CM) stretch, which are powerful stimuli for atrial remodeling. We have shown that the proinflammatory and mechanosensitive cytokine tumor necrosis factor (TNF) is a key mediator of stretch-related atrial remodeling and AF. Hypothesis: As TNF is a critical factor mediating fibrosis, hypertrophy, inflammation, and arrhythmias in CVD, we hypothesized that targeting TNF-dependent signaling may offer a novel therapeutic target in AF patients. Methods: We created an aortic regurgitation (AR) mouse model of volume overload characterized by elevated left ventricular end diastolic (LVEDPs) and atrial pressures. To examine TNF-dependent AF pathogenesis in AR, the impact of Tnf excision in atrial CMs (Cre-recombinase expression controlled by an Nppa promoter) and pharmacological TNF inhibition with Etanercept (twice-weekly, 2.5 mg/kg) beginning 2-days (early) or 1-week (delayed) post-AR in CD1 mice were examined. Cardiac structural, functional, and electrophysiological properties were assessed using echo, pressure telemetry, immunohistochemistry, in vivo intracardiacs, and ex vivo optical mapping of AF. Results: Four weeks of AR resulted in chronically elevated LVEDPs and progressive LV dilatation, functional impairment, and hypertrophy in the absence of ventricular arrhythmias with or without TNF inhibition compared to SHAM mice. In atria, AR resulted in both in vivo (8/11, 73%) and ex vivo (5/8, 63%) AF inducibility, which was associated with hypertrophy, fibrosis, and macrophage infiltration (F4/80 + ) as well as decreased conduction velocity and atrial effective refractory periods. Importantly, atrial CM-specific Tnf excision (n=10) and both early (n=8) and delayed (n=6) pharmacological TNF inhibition attenuated AR-induced adverse atrial remodeling and protected against AF inducibility. Conclusions: AF pathogenesis and vulnerability with AR requires TNF, suggesting TNF is an important therapeutic target for the prevention and treatment of AF linked to elevated atrial pressures.
Abstract 14447: Multi-Center Evaluation of Stress Myocardial Blood Flow by Cardiac Magnetic Resonance in Known and Suspected Ischemic Heart Disease: Preliminary Findings From the AQUA-MBF Initiative
Authors: Shuo Wang, Haonan Wang, Mitchel Benovoy, Ming-Yen Ng, Paul Kim, Amita Singh, Hena Patel, Ibrahim Saeed, Gianluca Pontone, Saima Mushtaq, Javier Urmeneta, Elizabeth Hillier, Lars C Gormsen, Christoffer Laustsen, Martin A Janich, Michael Salerno, Alexander Hirsch, Mark Lubberink, Alicia Maceira, Jose Monmeneu, Aju P Pazhenkottil, Prashant Nagpal, Silke Friedrich, Joseph Gutbrod, Caroline Flournoy, Yuko Tada, Sin Tsun Hei, Ambrose Ho Tung Fong, Ka Man Carmen Cheng, Victor K Goh, Simon Madsen, Andrew E Arai, Matthias G Friedrich, Amit R Patel
Journal: Circulation (2022)

Introduction: Quantitative myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) in several mostly small, single-center studies. The AQUA-MBF ( A ssessment of QUA ntitative MBF ) study is a multicenter initiative involving 16 centers. Hypothesis: The goal of this sub-study is to determine if MBF can differentiate CAD, CMD, and normal volunteers in this multicenter setting. Methods: We present data from 53 subjects (15 with CAD, 20 at risk for CMD and 18 controls) who underwent vasodilator stress CMR (Figure) using 1.5T and 3.0T MR scanners (General Electric). At risk for CMD was defined as having diabetes and 2 other risk factors in absence of ≥50% stenosis based on coronary CT. CAD was defined as the presence of stenosis ≥70% based on invasive coronary angiography. Stress perfusion images were acquired using the dual sequence technique. Stress MBF was measured in each of the 16 AHA segments using Fermi deconvolution (Circle Cvi42). In the CAD group, each segment was further classified as having late gadolinium enhancement (LGE), supplied by CAD, or a normal remote territory. The means of the 5 groups were compared using one-way analysis of variance. Results: The segmental stress MBF (ml/g/min) for the 5 groups are shown in figure. Compared to the normal group, segmental stress MBF in 4 disease groups were significantly lower (p&lt;0.001). Segmental MBF in those at risk for CMD was lower than normal segments and greater than CAD segments (p&lt;0.001). LGE and CAD segments had the lowest stress MBF but similar to each other (p=0.9). Conclusions: In this multicenter study, we show that quantification of MBF using the dual sequence stress perfusion CMR technique can differentiate diseased from healthy myocardium and also between obstructive CAD and those at risk for CMD.
Abstract 15181: PET/CT Imaging for Evaluating Inflammation in Rapamycin Coated Tissue-Engineered Arterial Grafts Implanted in an Ovine Model
Authors: Ting-heng Chou, Yuichi Matsuzaki, Ryuma Iwaki, Anudari Ulziibayar, christopher breuer, Toshiharu Shinoka, Mitchel R Stacy
Journal: Circulation (2022)

Introduction: Small diameter tissue-engineered arterial grafts (TEAGs) conjugated with rapamycin may improve TEAG outcomes by reducing early post-implant inflammatory responses, thereby improving rates of TEAG patency. Therefore, the objective of this study was to apply in vivo PET/CT imaging to compare inflammation and patency of TEAGs conjugated with or without rapamycin. We hypothesized that rapamycin-coated TEAGs would have reduced inflammation and improved patency rates that could be evaluated during a single imaging session using 18 F-FDG PET/CT imaging. Methods: Rapamycin coated (n=3) and non-rapamycin coated (n=3) TEAGs were unilaterally implanted in the carotid artery of juvenile lambs. Flourine-18 ( 18 F)-fluorodeoxyglucose (FDG) PET/CT imaging was performed 8 weeks after TEAG implantation to quantify inflammation of the graft, which was expressed as the maximum standardized uptake value (SUV max ) in the graft. Graft patency was assessed using co-registered CT angiography imaging. In vivo PET/CT imaging results were further evaluated by ex vivo gamma counting of 18 F-FDG uptake in TEAG tissue. Results: In vivo PET/CT detected qualitative and quantitative differences in inflammation between non-drug coated and drug coated TEAGs (SUV max : 6.18±1.67 vs, 4.25±0.81; p=0.1). Differences in inflammation between groups were significant when evaluating results of ex vivo gamma counting of 18 F-FDG uptake (% Injected dose/g: 0.86±0.10 vs, 0.50±0.010; p=0.003). Additionally, CT angiography demonstrated that all rapamycin-coated TEAGs were patent (3/3) at 8 weeks post-implant whereas only one non-drug coated TEAG remained patent (1/3). Conclusions: Conjugation of TEAGs with rapamycin prevents excessive inflammation in the early months after implantation and maintains graft patency. PET/CT offers a translatable imaging approach that allows for combined in vivo assessment of the functional and anatomical characteristics of TEAGs and may assist in optimizing scaffold design for next-generation TEAGs.
Abstract 15148: Contemporary Trends of Antibacterial Envelope Use to Prevent Cardiac Implantable Device Infection: Insights From the National Readmission Database
Authors: Islam Shatla, Mark Mujer, Preston Baker, Besher Kashlan, Zachary Pieters, Ahmed Elkaryoni, Alan P Wimmer
Journal: Circulation (2022)

Introduction: Local antibiotic delivery using an antibacterial envelope (AE) was shown to reduce major cardiac implantable electronic devices (CIEDs) infections in a controlled trial. We sought to assess the effect of AE use on CIED infection rates in subsequent clinical practice in the U.S. Methods: Using the Nationwide Readmissions Database and ICD 9/10-PCS codes, we identified patients who had a CIED implanted between 2010 and 2018. Patients were stratified according to the use of an AE. Outcomes were CIED infection rates as well as trends and predictors of AE use. Results: A total of 866,245 patients underwent CIED implantation between 2010 and 2018, with 8489 (1.0%) having an AE implanted during the same index admission. AE use showed an increasing pattern from 0.2% in 2012 up to 3.3% in 2018, p&lt;0.001. After excluding the last 6 months of each calendar year to allow for 6 months of follow-up data, a total 438,299 patients had a CIED implanted with 3938 (0.9%) receiving an AE. The rate of CIED related infection during 6-months post-implantation was lower among patients who had an AE (1.2% vs. 2.2, P&lt;0.001), and this difference persisted after adjustment using a multivariable regression model (OR, 0.53; 95% CI: 0.39-0.71, P&lt;0.001). Some patient factors (hypertension, heart failure, chronic kidney disease, atrial fibrillation and obesity), and hospital characteristics were independent predictors of increased likelihood of AE use during CIED placement (Table 1). Conclusions: There is an up-trending pattern of AE use during CIED implantation. The use of these envelopes is associated with a lower risk of CIED related infection.
Abstract 15812: Assessing the Effect of the Unos Heart Allocation Policy Change on Ohtx and Lvad Access and Outcomes
Authors: Daniel K Fox, RJ Waken, Erika Fanous, Fengxian Wang, Jonathan Wolfe, Keenan Robbins, Karen E Joynt Maddox
Journal: Circulation (2022)

Introduction: In October 2018, the heart allocation policy for adult heart transplant (OHTx) in the United States was changed, with the goal of reducing waitlist mortality and providing broader sharing of donor organs within the United States. The aim of this study was to assess the effect of this policy change on access to OHTx vs LVAD, overall and among key sociodemographic subgroups, in the US from 2016 to 2019. Hypothesis: We hypothesized that the UNOS heart allocation policy would increase OHTx volume overall as well as use of temporary mechanical circulatory support. Methods: We identified all patients receiving OHTx or LVAD between 2016-2019 using the National Inpatient Sample. Controlling for medical comorbidities, trends over time, and within hospital-year effects, we fit a dynamic logistic regression model to evaluate patient and hospital factors associated with receiving OHTx vs LVAD pre- versus post-policy change. Results: We identified 2264 patients who received OHTx and 3157 who received LVADs during the study period. Overall, there was a 4.16% increase in OHTx receipt, compared to LVAD, in the post-period (p=0.006). Among OHTx recipients, the frequency of use of tMCS changed from 15.61% in the pre period to 42.55% in the post period (p-value &lt; 0.0001). While the policy change was associated with differences in the odds of receiving an OHTx versus LVAD between different regions of the country, there were no significant changes based on age, gender, race/ethnicity, insurance status, or rurality. Conclusions: The UNOS policy change on access to OHTx was associated with slightly higher rates of OHTx overall, and higher rates of use of temporary support prior to transplant, but no differential change in access among key demographic groups. Shifts in regional allocation were not significant overall, though certain regions appeared to have a relative increase in their use of OHTx.
Abstract 230: Spinal Cord Injury In A 14 Days Survival Rat Model Of 6 And 8 Min Of Ventricular Fibrillation Cardiac Arrest, Resuscitated With Conventional Chest Compression
Authors: Wolfgang Weihs, Alexandra M Warenits, Ingrid A Magnet, Matthias Müller, Moritz Koch, Szinovatz Alexander, Michael Holzer, Sandra Högler
Journal: Circulation (2022)

Introduction: Impact of global ischemia and reperfusion on brain in resuscitation animal models is well investigated. Investigations on vulnerability of spinal cord in such models are rarely reported. We investigated the spinal cord in a cardiopulmonary resuscitation ventricular fibrillation cardiac arrest (VFCA) rat model and hypothesized that an untreated CA of 6 and 8 min will lead to histological damage and dysfunction in the resuscitated animal′s spinal cord, depending on CA duration. Methods: Adult male Sprague-Dawley rats (350-450 g) were subjected to 6 (n=8) or 8 min (n=14) of VFCA and resuscitated with conventional chest compressions with a thumper device, mechanical ventilation and drugs (epinephrine, bicarbonate, heparin). After defibrillation and ROSC, rats survived for 14 days. The spinal cord was removed from the spine after fixation in formalin and embedded in paraffin. Transverse sections of cervical, thoracic and lumbar spinal cord were stained with hematoxylin and eosin (HE). Immunohistochemistry was performed with antibodies against GFAP for astrocytes and Iba1 for microglia. Sections were evaluated by a pathologist blinded to treatment regimens, and compared to sham animals (n=5). Results: Resuscitated animals showed high mortality; after 6 min CA four animals and after 8 min CA eleven animals died before endpoint. Surviving animals showed focal bilateral symmetrical loss of neurons and distinct gliosis in the gray matter of the thoracic spinal cord level with the central canal. Similar lesions were detected in other segments of the spinal cord, but were located predominantly in the ventral horn of the spinal cord. These lesions were accompanied by dilated myelin sheaths in the white matter. Immunohistochemistry showed activation of astrocytes and microglia in the damaged regions. There were no differences detectable between animals subjected to 6 or 8 min VFCA. Sham animals showed no lesions in the spinal cord. Conclusions: We found consistent histological damage in the spinal cords of rats resuscitated after 6 and 8 min untreated VFCA with CPR after 14 days survival but without clinical symptoms in these animals. However, similar lesions might be cause of paralysis and urinary retention found in animals that died before endpoint.
Abstract 15534: Pericardial Effusion in People With HIV in the Era of Antiretroviral Therapy
Authors: Karla Inestroza, Vanessa Hurtado, Michaela Larson, Ryan Severdija, Sanjana Satish, Maria L Alcaide, Barry E Hurwitz, Catherine Boulanger, Dushyantha Jayaweera, Alexis Powell, Claudia Martinez
Journal: Circulation (2022)

Introduction: Pericardial effusion was previously described as one of the most common forms of cardiovascular involvement in People with HIV (PWH). The presence of pericardial effusion was considered a marker of advanced HIV infection and associated with a low CD4 cell count. This study describes the incidence and association of pericardial disease with HIV-related factors in an era of wider availability of antiretroviral therapy (ART). Methods: A retrospective chart review was performed of patients who received HIV care at the University of Miami/Jackson Memorial Hospital between 2017-2019 with an available echocardiogram (n=396). We stratified patients according to the presence (n=51) or absence of pericardial effusion (n=345) and compared demographic, clinical, imaging, and laboratory data. A p-value &lt;0.05 was considered statistically significant. Results: We found a prevalence of pericardial effusion in PWH of 4.5%. There was no statistically significant difference in age, gender, or race between groups. PWH with pericardial effusion had higher creatinine (2.1 mg/dL vs. 1.6 mg/dL, p=0.025) and pro-BNP (12,088 pg/mL vs. 6364 pg/mL, p=0.021) levels, were more likely to have chronic kidney disease (43.1% vs. 18%, p&lt;0.001), tricuspid regurgitation (64.6% vs. 44.2%, p=0.009), and mitral regurgitation (60.8% vs. 35.9%, p&lt;0.001) compared to PWH without pericardial effusion. There was no difference in CD4 count, CD8 count, viral load, length on ART, or history of tuberculosis between groups. Conclusions: We report a lower prevalence of pericardial effusion in PWH than previous results before the wide availability of ART (around 11%). In PWH with pericardial effusion, we found no association with HIV-related factors or length on ART. In this population, pericardial effusion was associated with comorbidities like chronic kidney disease and valvular abnormalities.
Abstract 14666: Coronary Arterial Calcification Influences Fractional Flow Reserve: Comparison of Guide Wire Type FFR With Vasodilator and FFRangio Without Vasodilator
Authors: Nobusada Funabashi, Kazuo Misumi
Journal: Circulation (2022)

Introduction: Fractional flow reserve (FFR) measures percutaneous coronary intervention (PCI) performance. FFR was determined by guide wire (GW)-type FFR. It is now evaluated by computed tomography (CT; FFRCT) or invasive coronary angiography (FFRangio; CathWorks, USA), whereby coronary arteries are traced on a conventional angiogram from three different angles to form three-dimensional images; the calculated FFR is FFRangio. In contrast to GW-type FFR, FFRangio does not need a vasodilator drug (e.g. nicorandil) load or GW. Hypothesis: Coronary calcification may influence the effect of vasodilator drugs, causing a difference between FFRangio and GW-type FFR depending on coronary calcium score (CCS). Methods: FFRangio and GW-type FFR (SJN, Zeon, ACIST) were simultaneously evaluated at catheter examinations in 11 coronary arteries from 9 patients before PCI (six males, mean age 72±11 years). Nicorandil (2 mg) was directly injected when measuring GW-type FFR. Cardiac CT was performed to measure CCS. Results: The correlation coefficients between FFR magnitude (=mean of FFRangio and GW-type FFR) and CCS in all vessels, and a vessel with FFR measurement, were -0.845 and -0.843, respectively. The correlation coefficients between difference in FFRangio minus GW-type FFR and CCS in all vessels, and a vessel with FFR measurement, were 0.627 and 0.752, respectively. The greater the CCS of both all vessels and a vessel in FFR measurements, the smaller the FFR. The greater the CCS of both all vessels and a vessel with FFR measurement, the greater the difference in FFRangio minus GW-type FFR (Figures). This may indicate the greater the CCS, the smaller the vasodilation effect of a direct nicorandil injection. Conclusions: Of GW-type FFR, FFRangio, and FFR CT, only GW-type FFR requires a vasodilator injection. Coronary arteries, known to cause blooming artifacts and impair the accuracy of FFRCT, also influence vasodilator effects, especially with borderline FFR (0.75-0.80).
Abstract 14903: Augmenting Prediction of Intracranial Aneurysm Rupture Status With Computed Velomics
Authors: Jingfeng Jiang, Seyedmostafa Rezaeitaleshmahalleh, Zonghan Lyu, Nan Mu, Charles Strother, Azam S Ahmed, joseph gemmete, aditya pandey
Journal: Circulation (2022)

Background Although race is a social construct without biological meaning, race significantly impacts health outcomes. Race is under-reported in clinical trials making it difficult to identify and address health inequities. In this study, we analyze studies pertaining to cerebrovascular accidents (CVA) with the primary purpose to assess the inclusion of racial data in CVA clinical trials. Our secondary purpose is to assess the representation of the various races in CVA clinical trials. Methods: This meta-analysis study consisted of CVA clinical trial data from ClinicalTrials.gov. Two researchers extracted data independently. Microsoft Excel was used for data collection and analysis. The search term “stroke” was used to search clinical trials from 1995-2021. The primary outcome is the prevalence of trials with racial data reported. The secondary outcome is the prevalence of each racial subgroup and gender subgroups among trials that report race data. Results: 7004 trials were identified using “stroke” as a search term. After excluding non-interventional trials, 468 trials remained. A sample of 115 trials were included in preliminary analyses. Out of the 115 trials, 50 studies (43.5%) did not report race. The 65 trials with racial data totaled 7368 participants. 38.7% were female and 61.3% were male. 46.2% of participants were White, 17.3% were Black and 33.8% a “combined other” category (Asian, American Indian, Native Hawaiian, other, and unknown/not reported). Of 12 trials with pharmacologic intervention, 41.7% did not report race. There were a total of 1485 participants from the seven trials with pharmacologic intervention, of which 47.2% were female and 52.7% male. Furthermore, 68.3% of participants were White, 7.5% were Black and 22.9% were the “combined other” category. Conclusions: Of the studies reviewed, 43.5% of stroke clinical trials and 41.7% of stroke studies with pharmacologic interventions did not report racial data. Moreover, women and non-White subjects were significantly underrepresented in the stroke clinical trials. The under-representation of women and non-White subjects in these clinical trials raises the concern regarding access to stroke clinical trials and the need to further study the reason behind these disparities.